The objectives of the proposed study are to delineate more clearly the pathophysiologic roles of endothelium in thrombosis as well as in hemostasis and maintenance of the normal blood fluidity. In order to attain these objectives a model system will be used in which human whole blood or platelet-rich plasma (PRP) will be pumped at controlled rates through the vein or artery of human umbilical cord segments. In this model, ultrastructural, functional, and biochemical studies of in situ endothelium can be carried out under controlled conditions of blood flow. Enzymatic dissection of the endothelial cell glycocalyx will be performed in an effort to determine the importance of this component of the cell in maintenance of the normal blood fluidity and in the usual nonreactivity of endothelium with blood soluble and cellular components. Damage to endothelium by a number of different mechanisms will be used to delineate the various possible pathophysiologic roles of altered endothelium in thrombosis. The uniqueness of the proposed model test system lies in the fact that human blood can be exposed to human endothelial cells in situ under a variety of flow conditions in a situation that permits various manipulations of both blood and endothelium. Few other model test systems permit such studies with human blood and endothelial cells. The successful use of the model system depends heavily on use of ultrastructural techniques and correlation of ultrastructural observations with functional and biochemical studies.